Management of immune thrombocytopenic purpura in children: Potential role of novel agents

Pediatric Drugs

Volumn 13, Issue 4, 2011, Pages 213-223

  Bredlau, Amy Lee ^a   Semple, John W ^b   Segel, George B ^c  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^b ST MICHAEL'S HOSPITAL   (Canada)

^c UNIVERSITY OF ROCHESTER   (United States)

Author keywords

Children; Glucocorticoids; Immune globulin; Immune thrombocytopenic purpura; Immunosuppressants; Rituximab; Thrombopoietin receptor agonists

Indexed keywords

AKR 501; DEXAMETHASONE; ELTROMBOPAG; FOSTAMATINIB; GLUCOCORTICOID; IMMUNOGLOBULIN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PREDNISONE; RHESUS ANTIBODY; RHESUS D ANTIBODY; RITUXIMAB; ROMIPLOSTIM; SYM 001; UNCLASSIFIED DRUG; VINCRISTINE;

ABDOMINAL PAIN; ALLERGIC REACTION; ANEMIA; ANXIETY; ARTHRALGIA; ARTICLE; ASEPTIC MENINGITIS; BEHAVIOR CHANGE; BONE DENSITY; CATARACT; CHICKENPOX; CHILL; CONSTIPATION; CUSHINGOID SYNDROME; DIABETES MELLITUS; DIARRHEA; DRUG MECHANISM; EPISTAXIS; FATIGUE; FEVER; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL SYMPTOM; GROWTH; HEADACHE; HEMOLYSIS; HUMAN; HYPERTENSION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; IMMUNITY; IMPAIRED GLUCOSE TOLERANCE; IMPOTENCE; INAPPROPRIATE VASOPRESSIN SECRETION; INJECTION SITE REACTION; INSOMNIA; JAW PAIN; KIDNEY FAILURE; LEUKOPENIA; MACULOPAPULAR RASH; MALAISE; MYELOFIBROSIS; NAUSEA; NAUSEA AND VOMITING; PATHOGENESIS; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; PRURITUS; SERUM SICKNESS; SIDE EFFECT; SPLENECTOMY; STOMACH DISTRESS; THROMBOCYTE COUNT; THROMBOCYTOPENIA; THROMBOEMBOLISM; THROMBOSIS; TREATMENT INDICATION; URTICARIA; VOMITING; WEIGHT GAIN;

ANIMALS; CHILD; DRUG COSTS; GLUCOCORTICOIDS; HUMANS; IMMUNOGLOBULINS, INTRAVENOUS; ISOANTIBODIES; PLATELET COUNT; PURPURA, THROMBOCYTOPENIC, IDIOPATHIC; SPLENECTOMY;

EID: 79959597551     PISSN: 11745878     EISSN: 11792019     Source Type: Journal    
DOI: 10.2165/11591640-000000000-00000     Document Type: Article

References (70)

1. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol 2010 Mar; 85 (3): 174-80
2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009 Mar 12; 113 (11): 2386-93
3. Zeller B, Rajantie J, Hedlund-Treutiger I, et al. Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease. Acta Paediatr 2005 Feb; 94 (2): 178-84 (Pubitemid 40343692)
4. Imbach P, Kuhne T, Muller D, et al. Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS). Pediatr Blood Cancer 2006 Mar; 46 (3): 351-6 (Pubitemid 43201852)
5. Sprague CC, Harrington WJ, Lange RD, et al. Platelet transfusions and the pathogenesis of idiopathic thrombocytopenic purpura. J Am Med Assoc 1952 Nov 22; 150 (12): 1193-8
6. Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura: physiologic, serologic and isotopic studies. Ann NY Acad Sci 1965 Jun 30; 124 (2): 499-542
7. Luiken GA, McMillan R, Lightsey AL, et al. Platelet-associated IgG in immune thrombocytopenic purpura. Blood 1977 Aug; 50 (2): 317-25 (Pubitemid 8140403)
8. Psaila B, Bussel JB. Refractory immune thrombocytopenic purpura: current strategies for investigation andmanagement. Br JHaematol 2008 Oct; 143 (1): 16-26
9. Deane S, Teuber SS, Gershwin ME. The geoepidemiology of immune thrombocytopenic purpura. Autoimmun Rev 2010 Mar; 9 (5): A342-9
10. Peerschke EI, Andemariam B, Yin W, et al. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura. Br J Haematol 2010 Feb; 148 (4): 638-45
11. Buchanan GR, Adix L. Current challenges in the management of children with idiopathic thrombocytopenic purpura. Pediatr Blood Cancer 2006 Oct 15; 47 (5 Suppl.): 681-4 (Pubitemid 44360027)
12. Segel GB, Feig SA. Controversies in the diagnosis and management of childhood acute immune thrombocytopenic purpura. Pediatr Blood Cancer 2009 Sep; 53 (3): 318-24
13. Semple JW. Infections, antigen-presenting cells, T cells, and immune tolerance: their role in the pathogenesis of immune thrombocytopenia. Hematol Oncol Clin North Am 2009 Dec; 23 (6): 1177-92
14. Semple JW, Provan D, Garvey MB, et al. Recent progress in understanding the pathogenesis of immune thrombocytopenia. Curr Opin Hematol 2010 Nov; 17 (6): 590-5
15. Yu J, Heck S, Patel V, et al. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood 2008 Aug 15; 112 (4): 1325-8
16. Cines DB, Bussel JB, Liebman HA, et al. The ITP syndrome: pathogenic and clinical diversity. Blood 2009 Jun 25; 113 (26): 6511-21
17. Olsson B, Andersson PO, Jernas M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. NatMed 2003 Sep; 9 (9): 1123-4 (Pubitemid 37173694)
18. Zhang X, Wang W, Cheng S, et al. 2,3-Diamino acid modifying 3Stetrahydroisoquinoline- 3-carboxylic acids: leading to a class of novel agents with highly unfolded conformation, selective in vitro anti-platelet aggregation and potent in vivo anti-thrombotic activity. Bioorg Med Chem 2010 Feb 15; 18 (4): 1536-54
19. Nugent D, McMillan R, Nichol JL, et al. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol 2009 Sep; 146 (6): 585-96
20. Chow L, Aslam R, Speck ER, et al. A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy. Blood 2010 Feb 11; 115 (6): 1247-53
21. Bolton-Maggs PH, Moon I. Assessment of UK practice for management of acute childhood idiopathic thrombocytopenic purpura against published guidelines. Lancet 1997 Aug 30; 350 (9078): 620-3 (Pubitemid 27367795)
22. Bussel JB, Zhang J, Tang S, et al. A randomized, double-blind, placebocontrolled phase II trial on the efficacy, safety and tolerability of E5501 (AKR501) in subjects with chronic immune thrombocytopenia (ITP). ASH Annual Meeting Abstracts. Blood 2010; 116 (21): 71
23. Beck JC, Burke MJ, Tolar J. Response of refractory immune thrombocytopenia after bone marrow transplantation to romiplostim. Pediatr Blood Cancer 2010 Mar; 54 (3): 490-1
24. Bussel JB. Update on eltrombopag for ITP. Oncology (Williston Park) 2009 Nov 30; 23 (13): 1177-8
25. Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009 Feb 21; 373 (9664): 641-8
26. Podolanczuk A, Lazarus AH, Crow AR, et al. Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood 2009 Apr 2; 113 (14): 3154-60
27. Tarantino MD, Bolton-Maggs PH. Update on the management of immune thrombocytopenic purpura in children. Curr Opin Hematol 2007 Sep; 14 (5): 526-34 (Pubitemid 47457645)
28. Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood 2007 Feb 15; 109 (4): 1401-7 (Pubitemid 46239570)
29. Kuhne T, Blanchette V, Buchanan GR, et al. Splenectomy in children with idiopathic thrombocytopenic purpura: a prospective study of 134 children from the Intercontinental Childhood ITP StudyGroup. Pediatr BloodCancer 2007 Nov; 49 (6): 829-34 (Pubitemid 47519522)
30. Tarantino MD, Young G, Bertolone SJ, et al. Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children. J Pediatr 2006 Apr; 148 (4): 489-94
31. Bennett CM, Rogers ZR, Kinnamon DD, et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood 2006 Apr 1; 107 (7): 2639-42
32. Rao VK, Dugan F, Dale JK, et al. Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome. Br J Haematol 2005 May; 129 (4): 534-8 (Pubitemid 40769903)
33. Calderwood S, Blanchette V, Doyle J, et al. Idiopathic thrombocytopenia and neutropenia in childhood. Am J Pediatr Hematol Oncol 1994 May; 16 (2): 95-101 (Pubitemid 24129018)
34. Ahn YS, Harrington WJ, Seelman RC, et al. Vincristine therapy of idiopathic and secondary thrombocytopenias. N Engl JMed 1974 Aug 22; 291 (8): 376-80
35. Carcao MD, Zipursky A, Butchart S, et al. Short-course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP). Acta Paediatr Suppl 1998 Jun; 424: 71-4 (Pubitemid 28410866)
36. Rossman MD, Chen E, Chien P, et al. Modulation of Fc gamma receptors on the human macrophage cell line U-937. Cell Immunol 1989 Apr 15; 120 (1): 174-87 (Pubitemid 19113721)
37. Kitchens CS, Pendergast JF. Human thrombocytopenia is associated with structural abnormalities of the endothelium that are ameliorated by glucocorticosteroid administration. Blood 1986 Jan; 67 (1): 203-6 (Pubitemid 16167033)
38. Mizutani H, Furubayashi T, Imai Y, et al. Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1. Blood 1992 Feb 15; 79 (4): 942-7
39. Huang HS, Sun DS, Lien TS, et al. Dendritic cells modulate platelet activity in IVIg-mediated amelioration of ITP in mice. Blood 2010 Dec 2; 116 (23): 5002-9
40. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010 Jan 14; 115 (2): 168-86
41. Kane I, Ragucci D, Shatat IF, et al. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura. Br J Haematol 2010 Apr; 149 (1): 79-83
42. De Mattia D, Del Vecchio GC, Russo G, et al. Management of chronic childhood immune thrombocytopenic purpura: AIEOP consensus guidelines. Acta Haematol 2010; 123 (2): 96-109
43. Wang J, Wiley JM, Luddy R, et al. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr 2005 Feb; 146 (2): 217-21 (Pubitemid 40202812)
44. Tamminga RY, Bruin MC. Rituximab treatment for symptomatic chronic ITP. Pediatr Blood Cancer 2006 Oct 15; 47 (5 Suppl.): 714-6 (Pubitemid 44360038)
45. Cooper N, Evangelista ML, Amadori S, et al. Should rituximab be used before or after splenectomy in patients with immune thrombocytopenic purpura? Curr Opin Hematol 2007 Nov; 14 (6): 642-6 (Pubitemid 47494081)
46. Blanchette V, Bolton-Maggs P. Childhood immune thrombocytopenic purpura: diagnosis and management. Pediatr Clin North Am 2008 Apr; 55 (2): 393-420, ix (Pubitemid 351442783)
47. Mueller BU, Bennett CM, Feldman HA, et al. One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab. Pediatr Blood Cancer 2009 Feb; 52 (2): 259-62
48. Wiberg FC, Rasmussen SK, Frandsen TP, et al. Production of target-specific recombinant human polyclonal antibodies in mammalian cells. Biotechnol Bioeng 2006 Jun 5; 94 (2): 396-405 (Pubitemid 43799538)
49. Bajpai M. Fostamatinib, a Syk inhibitor prodrug for the treatment of inflammatory diseases. IDrugs 2009 Mar; 12 (3): 174-85
50. Dameshek W, Miller EB. Themegakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. Blood 1946 Jan; 1: 27-50
51. McMillan R, Wang L, Tomer A, et al. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004 Feb 15; 103 (4): 1364-9 (Pubitemid 38168649)
52. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011 Jan 29; 377 (9763): 393-402
53. Gernsheimer TB, George JN, Aledort LM, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J ThrombHaemost 2010 Jun; 8 (6): 1372-82
54. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008 Feb 2; 371 (9610): 395-403 (Pubitemid 351181334)
55. Gernsheimer T. Chronic idiopathic thrombocytopenic purpura: mechanisms of pathogenesis. Oncologist 2009; 14: 12-21
56. Gernsheimer TB. The pathophysiology of ITP revisited: ineffective thrombopoiesis and the emerging role of thrombopoietin receptor agonists in the management of chronic immune thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program 2008; 219-26
57. Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009 Mar 5; 113 (10): 2161-71
58. Erhardt JA, Erickson-Miller CL, Aivado M, et al. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp Hematol 2009 Sep; 37 (9): 1030-7
59. Saleh MN, Bussel JB, Cheng G, et al. Long-term treatment of chronic immune thrombocytopenic purpura with oral eltrombopag: results from the EXTEND study [abstract]. ASH Annual Meeting Abstracts. ASH Annual Meeting Abstracts. Blood 2009; 114 (22): 682
60. Erickson-Miller CL, Delorme E, Tian SS, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells 2009 Feb; 27 (2): 424-30
61. Desjardins RE, Tempel DL, Lucek R, et al. Single and multiple oral doses of AKR-501 (YM477) increase the platelet count in healthy volunteers [abstract]. ASH Annual Meeting Abstracts. ASH Annual Meeting Abstracts. Blood 2006; 108 (11): 477
62. Bussel JB, Zhang J, Tang S, et al. Efficacy, safety and tolerability of E5501 (AKR501) in a 6-month extension study in subjects with chronic immune thrombocytopenia (ITP) [abstract]. ASH Annual Meeting Abstracts. Blood 2010; 116 (21): 3695
63. Boruchov DM, Gururangan S, Driscoll MC, et al. Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP). Blood 2007 Nov 15; 110 (10): 3526-31 (Pubitemid 350159616)
64. Williams JA, Boxer LA. Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents. J Pediatr Hematol Oncol 2003 Mar; 25 (3): 232-5 (Pubitemid 36292839)
65. Zhang WG, Ji L, Cao XM, et al. Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura. Acta Pharmacol Sin 2005 May; 26 (5): 598-602 (Pubitemid 40676172)
66. Provan D, Moss AJ, Newland AC, et al. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol 2006 Jan; 81 (1): 19-25 (Pubitemid 43077209)
67. Russo G, Miraglia V, Branciforte F, et al. Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study. Pediatr Blood Cancer 2011 Feb; 56(2): 273-8
68. Treepongkaruna S, Sirachainan N, Kanjanapongkul S, et al. Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial. Pediatr Blood Cancer 2009 Jul; 53 (1): 72-7
69. Zaja F, BaccaraniM,Mazza P, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasonemonotherapy in adults with primary immune thrombocytopenia. Blood 2010 Apr 8; 115 (14): 2755-62
70. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011 Mar; 117 (16): 4190-207